The medical device field is in constant need of improved, inexpensive, elastomeric material that combine biocompatibility with such elastomeric properties as flexibility, durability, and tear strength. In particular, with the risk of blood-borne infection to health care workers, such as AIDS and hepatitis, being such a serious concern today, there is a critical demand for improved, inexpensive, biocompatible elastomers for sealing and access applications for human systems. There is a particular demand for such elastomers in extracorporeal tubing systems, such as human infusion and dialysis systems.
The present invention provides means for improving elastomeric materials while maintaining biocompatibility. The present invention provides methods for treating elastomeric material, particularly inexpensive natural and synthetic rubbers, which significantly improves ease of use while decreasing the amount of undesirable organics that are extractable from the elastomer into physiological fluids. The methods provided minimize deterioration of desirable elastomeric properties of the material and instead result in improvement of certain properties. The methods provided are particularly useful for applications to penetrable elastomeric materials including applications of such materials in extracorporeal tubing systems.
One method involves deep cleaning of elastomers employing organic solvents. A second method involves introduction of lubricating fluids into elastomers to give more easily penetrable materials. A third method involves infusion of the elastomer with a solution of a lubricating fluid in an organic solvent to give internally-lubricated elastomeric materials having significantly lower levels of extractable organics.
The present invention also provides means for improving the integrity of apparatus used for the infusion, monitoring or withdrawal of fluid in extracorporeal tubing systems by using improved elastomers in the septa of such devices. Currently, such systems are single patient, single use disposable devices intended for relatively short-term use up to several days. A needle-penetrable barrier functions as the most convenient means for introducing or withdrawing fluids from a patient's extracorporeal tubing system. The penetrable barrier, or septum, allows access to the system while protecting the patient from external contamination and protecting others from contact with potentially dangerous patient body fluids.
The useful lifetime of any septum in the apparatus is decreased by repeated piercing which results in coring, tearing and abrasion of the septum. After repeated use, the septum can also leak, compromising the integrity of the system, and may release debris into the system. The useful lifetime of extracorporeal tubing apparatus can be increased by employing a septum material that has improved resistance to coring, tearing and abrasion.
Septa currently employed in biomedical applications are typically natural rubber, synthetic polyisoprene rubber or silicone rubber. These materials are typically difficult to penetrate and display rapid deterioration on repeated piercing with the large gauge needles (18 and 20 gauge) that are often used for blood sampling and fluid infusion.
It is desirable that septa allow penetration for fluid access with minimum force of insertion to lessen the danger of either damage to the apparatus or injury to the patient or health care worker while maintaining a sealed system. One well known prior art solution for reducing the risk to patients and health care workers is to blunt the needle that penetrates the septum such that it is not sharp enough to penetrate skin unless an undue force is exerted on it. This has required that the septum be pre-slit or lanced, and provisions made for guiding the blunt needle into the correct orientation on the septum. This solution has failed, at least in part, because the blunt needle tends to gall or core the septum material. As a result, small pieces of septum material are potentially released into the patient's blood stream. This is particularly worrisome where septum material is released into a patient's venous blood stream because the contaminating material may potentially enter a patient's brain via the venous pathway.
The inventors have found that significantly improved elastomeric septa for biomedical applications can be produced by dispersing a lubricating oil, such as a silicone oil or a mineral oil, throughout an elastomeric material, such as a natural or synthetic rubber. It is desirable for the resulting composition to have a Shore A durometer hardness in the range of 15 to 40. The resulting internally lubricated septa display dramatically lowered resistance to penetration with surprisingly improved resistance to deterioration on piercing, improved resealing properties, and improved tearing and coring resistance. In addition, these internally lubricated septa display surprisingly lowered levels of undesirable organic extractables, making them even more attractive for medical device applications.
In one embodiment, the inventors have found that using a thermoplastic elastomer, a styrene-ethylene/butylene-styrene block copolymer internally lubricated with a silicone oil having a Shore A durometer hardness in the range of 15 to 40, and sold under the name C-FLEX.RTM. by Consolidated Polymer Technologies, Inc., to construct septa offers significant advantages over the prior art. Using this thermoplastic elastomer allows the septum to form an un-pierced, continuous seal through which a blunt or sharp needle can be penetrated. Un-pierced is herein defined as not having a preformed opening prior to the first needle penetration. The septum will then form a transient opening around the needle allowing fluid to be removed from, added to and/or monitored in the extracorporeal tubing system. After the needle is removed from the septum, the transient opening reseals automatically once again forming a continuous seal with satisfactory leak resistance for the useful life of the septum. The useful life of the septum is defined as at least six penetrations. Due to this automatic resealing characteristic, the septum of the thermoplastic elastomeric embodiment of the present invention is defined as self-sealing.
The thermoplastic elastomeric embodiment or second preferred embodiment of the present invention, therefore, does not require pre-slitting or lancing during manufacture. Furthermore, the thermoplastic seal may be manufactured using plastic injection molding, significantly reducing the cost and increasing the ease of manufacture. The invention's configuration also renders the septum/needle alignment notably less critical than for the prior art. The invention is therefore safer and easier to use.
Attempts to improve the design of septa for extracorporeal tubing systems have included:
U.S. Pat. No. 5,324,256 (1994) and U.S. Pat. No. 5,215,537 (1993) to Lynn et al. disclose elastomeric septa for coupling intravenous conduits. Lynn ('256) discloses a blunt cannula surrounded by a shroud that is sharp enough to penetrate an unperforated rubber septa but not sharp enough to penetrate human skin when a casual force is exerted on it. Lynn ('537) discloses an embodiment that provides a septum having a continuous un-pierced surface with a weakened core. A blunt cannula can then be forced through the septum at the weakened core. The thermoplastic elastomeric embodiment of the present invention, on the other hand, is composed of a uniformly strong internally lubricated thermoplastic elastomer that does not require a weakened core or sharpened cannula for penetration.
U.S. Pat. No. 5,209,737 (1993) to Ritchart et al. discloses a septum for surgical trocars. The disclosed septum is composed of C-FLEX.RTM., the same thermoplastic elastomer used in the second preferred embodiment of the present invention. The disclosed '737 invention, however, does not disclose an unpierced septum, but rather provides the C-FLEX.RTM. septum with an adjustable orifice for receiving and sealing around a surgical instrument. The orifice is adjusted via a lever system. The preferred embodiment of the present invention, employing C-FLEX.RTM., does not require an orifice and resealing means. The C-FLEX.RTM. preferred embodiment of the present invention is initially manufactured as a continuous unpierced seal and automatically reseals once the probe or cannula is removed.
U.S. Pat. No. 5,207,656 (1993) to Kranys discloses a medical instrument valve, such as a hemostasis valve in a catheter introducer, having an un-pierced, foamed, elastomeric septum for receiving a solid elongated member, such as a guide wire. Kranys ('656) does not disclose lubricating the elastomeric material of the septum itself. Rather, fluid, including lubricating fluid, may be contained in the cells of the foam. Furthermore, the Kranys ('656) invention is designed to receive solid elongated members for a limited number of penetrations.
The present invention comprises an internally lubricated elastomeric septum for use with cannulas that is not foamed and, therefore, does not contain internal cells. Using a foam with a hollow member, such as a cannula or conventional needle, could result in serious coring problems, particularly with large gauge needles. Foamed elastomers also have a lower tensile strengths than internally lubricated elastomers. The lower tensile strength of foam renders it less durable and resealable than an internally lubricated solid, as well as increasing the risk of galling and coring. Furthermore, it is very possible that blood could enter the cells of a foam septum, coagulate and be released back into the blood stream when the foam septum is penetrated again, resulting in thrombosis problems if repeatedly penetrated.
U.S. Pat. No. 5,080,654 (1992) to Picha et al. discloses a fluid injection device for an intravenous delivery system having an access port with a closure element, where the closure element has a preformed central passage for receiving a blunt injection probe. The elastomeric septa of the present invention are un-pierced and do not require a preformed passage for receiving a blunt probe.
U.S. Pat. No. 4,496,348 (1985) to Genese et al. discloses a venipuncture device having a solid, elastic septum which is penetrable by a sharpened tip. Upon removal of the sharpened tip, a spring-loaded compression mechanism applies a compressive force against the elastic septum, thereby resealing the opening. The septa of the present invention may be used with a blunt cannula and do not require a spring-loaded compression device for resealing. The septa of the present invention are self-sealing.
U.S. Pat. No. 4,935,010 (1990) to Cox et al. discloses a valve having an elastomeric septa having a preformed zone of weakness for receiving a blunt cannula. The disclosed zone of weakness is a cruciform cut that extends completely or partially through the length of the septa. In contrast, the present invention provides an un-pierced, uniformly strong, continuous septum that is penetrable by a blunt or sharp needle.
Attempts to improve the resealability of elastomeric sealing members, such as septa, have included:
U.S. Pat. No. 3,853,129 of Spademan in which non-uniform stress is induced normal to the longitudinal axis of the septum to facilitate resealing; U.S. Pat. No. 5,135,489 of Jepson et al. in which axially directed force is applied to reseal a pre-split septum; and U.S. Pat. No. 4,954,149 of Fullerman in which a septum having a pre-cut annular injection passage is sealed by a duckbill seal.
Attempts to provide improved materials for penetrable rubber closures have included:
U.S. Pat. No. 5,082,875 of Tajima et al. which describes synthetic rubber compositions containing high molecular weight polyethylene (HMPE, MW 10.sup.6 to 10.sup.9) which are said to have good tensile strength and elongation properties;
U.S. Pat. No. 4,684,672 of Buchanan et al. which relates to high tear-strength natural or synthetic rubber compositions comprising high density polyolefin, a filler and a multi-functional activator to cross-link the rubber and polyolefin; and
U.S. Pat. Nos. 4,810,752 and 4,978,714 of Bayan et al. which describe elastomeric compositions with low hardness, low coefficients of friction, and reduced stickiness which provide good barriers to moisture and oxygen. The composition combines a dynamically vulcanized butyl rubber with uncured organopolysiloxane grafted EPDM polymers.
The following references may also be considered relevant to the present invention:
U.S. Pat. No. 5,177,139 to Klaar discloses a composition useful as a sealing strip or molding in the construction industry. The composition is composed of polyolefin rubber and polyethylene having a critical melt flow index value and a mineral oil. The composition is said to have improved elongation and tensile strength with respect to application as a roof sealing strip.
U.S. Pat. No. 4,123,409 of Kaeble describes a thermoplastic sealing material for contact with animal tissue. An elastomeric material with thixotropic properties combining a high molecular weight non-volatile oil in at least a ratio of 1 to 1 with a block copolymer is described. The material is said to be flexible and conformable to the skin and to provide a wetting-type property. Thermoplastic block copolymers having polystyrene end blocks and butadiene or isoprene intermediate blocks are combined with a hydrocarbon oil, e.g., mineral oil, compatible with the intermediate block. Thermoplastic block copolymers having polyalpha-methylstyrene end blocks and polydimethylsiloxane intermediate blocks are combined with silicone oil. Molded articles made with these materials are said to combine conformability and flexibility with adherence strength and resistance to tearing.
U.S. Pat. No. 5,143,963 of Sterling et al. describes elastomeric compositions having fluorocarbon oils, gums or greases dispersed there through. The compositions have fluorocarbon-like surface properties which are said to be advantageous for medical applications, having superior biocompatibility for medical tubing, implants, etc.
U.S. Pat. No. 4,386,179 (1983) to Sterling, and 4,481,323 to Sterling relate to thermoplastic elastomer compositions having a uniformly dispersed (0.1 to 8%, or 0.1 to 12%) polysiloxane or silicone oil throughout the composition. These compositions are said to be useful in medical applications, for example, as inflatable cuffs or balloons in endotracheal devices. Articles made from these materials are said to have a smooth surface, like a silicone polymer, which is less irritating for skin contact. Compositions include hydrocarbon block copolymers, such as styrene-ethylene-butylene-styrene copolymers, to which silicone oil and optionally mineral oil are added. The disclosures discuss the partial migration of the silicone to the surface of the material. Related U.S. Pat. No. 5,511,354 (1985) to Sterling, derived from a divisional application of '179 and claims the use of the material disclosed in '179 for use as an inflatable cuff, particularly an inflatable cuff surrounding the shaft of an endotracheal tube. Related U.S. Pat. No. 4,578,413 also to Sterling, describes polymeric tubing composed of the same thermoplastic elastomer compositions useful for medical applications, particularly for tubing with improved flex-life, low spallation in roller-type applications, and decreased debris production. The disclosures of U.S. Pat. Nos. 4,386,179 (1983), 4,481,323 (1984), 4,511,354 (1985) and 4,578,413 (1986) to Sterling and U.S. Pat. No. 4,613,640 (1986) to Deisler are herein incorporated by reference in their entirety.
In particular, Sterling ('179) describes a composition including an elastomeric thermoplastic block copolymer having polysiloxane (0.1-8%) dispersed throughout. The composition is formed by melting elastomeric crumbs mixed with polysiloxane and subjecting the melted mixture to a shearing pressure, for example by extruding under pressure of 2500 p.s.i. or greater. The pressurized extruding process appears necessary to achieve the disclosed properties. Those disclosed properties include the ability to be extruded into extremely thins sheets (0.005 inch or less), a high degree of elasticity, and a greater concentration of polysiloxane at the immediate surface of the material than internally. The disclosed medical uses include a balloon cuff for an endotracheal tube and a cellular sponge like material for padding wounds. Flexibility and capacity to be extruded into thin sheets appear to be the most important characteristics of the composition.
Surprisingly, we have found that certain variations on compositions of the internally lubricated thermoplastic elastomer generally disclosed in '179, '323, '354 and '413 to Sterling and in '640 to Diesler, are useful as penetrable septa in applications that require multiple penetrations. To be useful for penetrable septa that will be penetrated multiple times, a chosen material should possess an appropriate amount of hardness for resealability to needle puncture, ease of penetration, flexibility, resistance to coring and galling, and tear strength. An appropriate hardness for resealability to needle puncture falls in the range of about 15 to about 40 on the Shore A durometer hardness scale. A material having a hardness in this range will not leak when penetrated at least six times at the same insertion site. Materials having a Shore A durometer hardness greater than about 40 are not likely to reseal adequately after puncture and, therefore, are likely to leak.
The disclosures of '179 and '354 do not disclose the Shore A durometer hardness of the claimed compositions, nor suggest that the claimed compositions would reseal after multiple punctures. The disclosure of '323 describes compositions having Shore A durometer hardnesses of at least 44 or greater. The disclosure of '413 describes compositions having Shore A durometer hardnesses of at least 50. Surprisingly, we have found that if certain compositions of the internally lubricated thermoplastic elastomer generally disclosed in '179, '323, '354 and '413 are modified to bring their Shore A hardness within the range of 15 to 40, they are easily penetrable, resistant to coring and galling and capable of withstanding repeated punctures without leakage.
It is also surprising that compositions generally disclosed in '179, '323, '354 and 413 are easily penetrable because the disclosures of these patents teach that the internal lubricant, polysiloxane, tends to concentrate at the immediate surface of the material rather than uniformly dispersing throughout the material. Furthermore, the disclosures of the Sterling patents do not suggest that the disclosed compositions or modifications thereof possess the combination of characteristics necessary for a penetrable septa that will be used in applications requiring multiple penetrations.
U.S. Pat. No. 4,613,640 (1986) to Deisler et al. discloses a composition comprising an elastomeric thermoplastic block copolymer, mineral oil and polysiloxane which is miscible in mineral oil. The composition is said to be an improvement compositions previously disclosed by Sterling in U.S. Pat. No. 4,386,179 (cited herein) and U.S. Pat. No. 4,481,323 (cited herein). The improvement is to increase the transparency of the material for use as container or tubing. Corresponding with these uses, the Deisler ('640) reports Shore A durometer hardnesses ranging from 49 to 70.
U.S. Pat. No. 4,177,182 of Ichikawa et al. relates to polyvinyl chloride resin compositions comprising 100 parts by weight of polyvinyl chloride series resin, 20-80 parts by weight of a plasticizer, and 0.2 to 7 parts by weight of silicone oil. The silicone oil is said to minimize the elution of the plasticizer from the resin. These resins are said to be well adapted for uses in food containers and medical products, particularly for the collection, preservation and administration of physiological solutions.
U.S. Pat. No. 3,034,509 of Bernstein et al. describes surgical tubing made with a polyethylene to which 0.5 to 1% by weight silicone oil has been added. The silicone oil is said to reduce toxic reaction to the tubing and to inhibit blood coagulation upon contact with the tubing.
U.S. Pat. No. 2,992,940 of Pace relates to elastomeric flexible cellular materials from polyisocyanates which are treated by external application of silicone oil or by injection of silicone oil into the cellular structure to eliminate internal tack.